B1 cells play an important role in the development of autoimmunity and lymphoid malignancy (Youinou, P. et al., Eur. J. of Clin. Invest., 23:139-150 (1993). B1 cells can be identified by the presence of small amounts of the pan-T cell marker, CD5, in conjunction with the typical B cell markers IgM, CD45R(B220), class II MHC, and Fc.gamma.R. However, they lack T cell markers such as CD3, CD4, and CD8. They also appear to be the B cell population that expresses the receptor for IL-5.
In humans, B1 cells are increased in frequency in many autoimmune conditions and are responsible for production of autoantibodies such as IgM rheumatoid factor. (Lydyard, P.M., et al., Immunol. Today, 8:37-38 (1987); Mix, E., et al., Clin. Exp. Immunol., 79:21-27 (1990); Munoz, A., et al., Clin. Exp. Immunol., 83:304-308 (1991); Mizutani, H., et al., Br. J. Haematol., 78:474-479 (1991); Jarvis, J. N., et al., Arthritis Rheum., 35:204-207 (1992); Hardy, R. R., et al., Science, 236:81-83 (1987)). In mice, B1 cells have been found to be the primary source of autoantibodies found in normal mice and autoimmune strains of mice, such as the NZBWF.sub.1 mouse strain (Hayakawa, K., et al., Proc. Natl. Acad. Sci, USA, 81:2494-2498 (1984); Hayakawa, K., et al., J. Exp. Med., 157:202-218 (1983); Stall, A. M., et al., Proc. Natl. Acad. Sci, USA, 85:7312-7316 (1988)).
In addition, B1 cells also appear to be the B cells responsible for chronic lymphocytic leukemia (CLL), the most common adult leukemia in Western societies and a malignancy often associated with autoimmunity. Approximately 95% of patients with CLL have leukemic cells that coexpress CD5 in conjunction with other B cell surface antigens (Royston, I., et al., J. Immunol., 125:725-731 (1980); Boumsell, L., et al., J. Exp. Med., 152:229-234 (1980)). This phenotype is not present on immature B lymphocytes in bone marrow nor on other "immature" B cell malignancies. Furthermore, unlike other leukemias, normal and leukemic B1 cells can express myeloid-associated markers such as CD11b, CD14, and CD15 (Morabito, F., et al., Blood, 70:1750-1757 (1987)). Murine B1 cells show increased longevity in vitro and often give rise to B cell lymphomas in aged mice (Braun, J., J. Immunol., 130:2113-2116 (1983); Lanier, L. L., et al., Immunogenetics, 16:367-371 (1982); Davidson, W. F., et al., J. Immunol., 133:744-753 (1984); Pennell, C. A., et al., Proc. Natl. Acad. Sci, USA, 82:3799-3803 (1985)).
Treatment of these B1 cell disorders generally involves the use of corticosteroids for autoimmune diseases and immunosuppressive chemotherapy and irradiation for CLL. These current treatments of B1 cell disorders are non-specific and result in a general suppression of a host's immune system.